Method of Laminating Absorbable Semi-Crystalline Polymeric Films

ABSTRACT

The invention relates to novel processes for the lamination of semi-crystalline, high-melting point, low glass transition polymeric films, which are extruded and subsequently laminated on various thermally sensitive substrates to form laminated medical device constructs in a specific time interval to allow low processing temperatures to avoid polymer film and/or substrate degradation or heat-related distortions. Also disclosed are laminated medical device constructs made from such processes.

FIELD OF THE INVENTION

The field of art to which this invention relates is novel methods forthe lamination of absorbable, semi-crystalline, high melting polymericfilms on various thermally sensitive substrates for absorbable andpartially absorbable medical applications.

BACKGROUND OF THE INVENTION

Synthetic absorbable polyesters are well known in the art. The termsabsorbable, bioabsorbable, bioresorbable, resorbable, biodegradable areused herein interchangeably. The open and patent literature particularlydescribe polymers and copolymers made from glycolide, L(−)-lactide,D(+)-lactide, meso-lactide, epsilon-caprolactone, p-dioxanone, andtrimethylene carbonate.

Medical devices in the form of polymeric films or a composite structurecontaining a substrate and a laminated film are known in the art andhave utility in a variety of surgical applications including tissuerepair, hernia repair, organ repair, etc.

Absorbable films and processes for forming such films from bioabsorbablepolymeric materials have also been described by various researchers overthe years, e.g., U.S. Pat. No. 7,943,683 B2, “Medical Devices ContainingOriented Films of Poly-4-hydroxybutyrate and Copolymers”; U.S. Pat. No.8,030,434 B2, “Polyester Film, Process for Producing the Same and UseThereof”; U.S. Pat. No. 4,942,087A, “Films of Wholly Aromatic Polyesterand Processes for Preparation Thereof”; U.S. Pat. No. 4,664,859A,“Process for Solvent Casting a Film”; and, U.S. Pat. No. 5,510,176A,“Polytetrafluoroethylene Porous Film”. Various conventionalmethodologies and processes are known and exist to produce polymericfilms. They include, but are not limited to, melt extrusion, solventcasting, and compression molding. However, not all polymers can beeasily converted to film products; additionally, different conversiontechniques have different challenges. In the case of melt extrusion, theresin must be thermally stable, exhibiting an appropriate meltviscosity, i.e., not too low so as to cause “dripping” and not too highso as to develop excessively high pressures in the extruder, causinginstability and non-uniform results. In the case of resins possessinglow glass transition temperatures, the dimensional stability of thefilms made therefrom may be very low if the polymer morphology includessome chain orientation. This is a great driving force for shrinkage anddistortion. To circumvent dimensional instability difficulties, thedevelopment of a certain amount of crystallinity in the film isadvantageous. The rate of crystallization is important in establishing arobust film extrusion process, while the overall level of crystallinityis important in achieving dimensional stability and good mechanicalproperties. It is known that a crystallinity level that is too low willresult in films which may distort upon ethylene oxide sterilization orupon exposure to even mildly elevated temperatures during processing,transportation, or storage. In certain surgical applications, it isdesirable for the final films to be strong with appropriate tearresistance, yet pliable enough to possess good handling characteristics.Examples of such surgical applications include hernia film-containingrepair patches requiring suturing and/or tacking as a means of fixationto the surrounding tissues, various film-based medical devices thatundergo extensive handling and manipulation prior to implantation, incases where the film is a load-bearing component, etc.

An absorbable polymer used to manufacture films must possess certainmelt and thermal properties, certain crystallization characteristics, aswell as certain mechanical and hydrolysis properties, if it is to besuitable for fabricating surgical film products by a melt extrusionprocess. In the case of films made by solution casting, the polymerresin needs to possess appropriate solubility in a suitable solvent.Suitable solvents advantageously have an appropriate vapor pressurecurve leading to suitable evaporation rates, and are generallynon-toxic. The polymer must then possess certain solubility andcrystallization characteristics, as well as certain mechanical andhydrolysis properties, if it is to be suitable for fabricating surgicalfilm products by a solvent casting process.

Methods of laminating a polymeric film on different substrates have beendescribed in the patent literature. For instance, U.S. Pat. No.8,349,354B2 (Andjelic) describes a hemostatic composite structure havingan absorbable fabric or non-woven substrate and continuous non-porouspolymeric film that is laminated on one major surface of the substrate.However, the film layer is limited to an amorphous polymeric material,or semi-crystalline polymeric material having a melting pointtemperature below 120° C.

For the lamination of polymeric films having a melting point temperaturesignificantly higher than 120° C. (e.g., around 200° C.), differentapproaches have been used and disclosed in the prior art, including theaddition of an adhesive layer between the high melting point polymericfilm and a substrate as described in U.S. Pat. Nos. 7,615,065 and8,821,585 B2. In the market place, the ETHICON PHYSIOMESH™ mesh deviceis a commercially available hernia mesh product that is made from anabsorbable polymer film (based on 75/25 Gly/Cap resin) coupled with anon-absorbable polypropylene mesh. To join the high melting pointpolymeric film onto the mesh, an interlayer of lower melting point poly(p-dioxanone)-based film (melting point of 110° C.) is used on bothsides of the mesh to glue these three structures together to form thecomposite structure. If no adhesive layer/film were used for bonding, ahigh temperature above 150° C. would be needed to bond the absorbablepolymer film to the mesh, resulting in distortion and shrinkage of themesh. On the other hand, the presence of an additional layer for bondingpurposes increases the risk of adverse tissue reactions (moredegradation products released such as free acids), biocompatibility, andincreases device stiffness; it also significantly increases productioncost and complicates the manufacture of such a medical device.

Similar to the technology mentioned above, U.S. Pat. No. 3,467,565Adescribes the lamination of a high melting plastic film, such as Nylon,onto a carrier web using a low melting plastic film, such aspolyethylene. The disclosure is silent with respect to using thistechnology on absorbable polymer systems.

A method for forming strong cross-laminated flat films described in U.S.Pat. No. 4,475,971A comprises composite, coextruded film structureshaving a higher melting point layer and a lower melting point layer. Thehigher melting point layer may be polyethylene, nylon, polyester orpolypropylene, while the lower melting point component is selected fromthe group consisting of an ethylene/vinyl acetate copolymer, a lowdensity polyethylene polymer and an ethylene/propylene copolymer. Again,the low melting point component as a glue is used on all non-absorbablecomponents.

U.S. Pat. No. 6,911,244B2 describes the encapsulated barrier forflexible films comprising a barrier layer made from a thermallysensitive material, preferably ethylene vinyl alcohol, and at least onesubstrate, preferably oriented polypropylene encapsulated by two or moreadhesive layers. The adhesive layers, in addition to having a bondingfunction may also protect the barrier material from high temperatures ofthe hardware and long residence times within the hardware.

US 20130001782A1 teaches a method utilizing a low melting thin metallicfilm for lamination of a high melting point soldering layer on athree-layered structure for fabrication of a semiconductor device.

A biodegradable mesh and film stent for use in blood vessels isdescribed in U.S. Pat. No. 5,629,077 comprising a sheet of a compositemesh material made from biodegradable high strength polymer fibersbonded together with a second biodegradable adhesive polymer, andlaminated on at least one side with a thin film of a third biodegradablepolymer. The lamination is achieved by heat bonding via a lowertemperature adhesive biodegradable layer, such as epsilon-caprolactoneor a low melting point temperature plurality of fibers in a meshstructure.

Laminated food packaging having a multilayered film structure and havinglow vapor and gas permeability is described in U.S. Pat. No. 3,932,693A.The structure comprises a base layer of an oriented polypropylene filmlaminated onto a layer of a vinylidene chloride polymer using a layer ofethylene/vinyl acetate copolymer film having vinyl acetate contentgreater than 10 percent by weight.

U.S. Pat. No. 4,119,481A describes a fusion laminated high-temperaturefabric made of amorphous silica fibers with a thermoplastic film madefrom vinyl, polyester or urethane polymers using high energy infra-redradiation. The high energy is preferentially absorbed in a short timeand space resulting in an increase in temperature sufficient to producethe desired degree of adhesion with the thermoplastic film. Althoughthis method of lamination does not require an additional adhesiveelement, the use of high energy radiation can cause degradation in caseswhere fabric and/or film are made from absorbable polymers.

A method of making laminated Nylon-based fabrics is described in U.S.Pat. No. 2,269,125A. The method provides for treating the fabric withwater for easier heat pressure bonding. The absorbed moisture lowerssignificantly the glass transition temperature and increases thermalconductivity of Nylon-based fibers allowing for the lower laminationtemperatures. However, the use of moisture with heat on absorbablepolymer structures would cause significant polymer degradation.

In summary, there is a strong, continuing need in this art for novelmethods that will effectively laminate high melting temperature,semi-crystalline absorbable films on various thermally sensitiveabsorbable or non-absorbable substrates without the need for anyadditional adhesive layer or any type of glue substance, includingmoisture. The lamination of thermally sensitive substrates needs to beconducted using low lamination temperatures, such as 120° C. or lower,to avoid chemical degradation and physical distortions and novel methodsare needed to provide for the lamination of such substrates.

SUMMARY OF THE INVENTION

Accordingly, novel lamination methods and laminated medical deviceconstructs are disclosed.

One aspect of the present invention is a method of manufacturing alaminated medical device construct. A semicrystalline polymer film isextruded, the polymer film having a melting point temperature of 140° orhigher, a glass transition temperature below 25° C., and acrystallinity, wherein said polymer film is crystallizable atroom/ambient conditions.

The polymer film is laminated to a thermally sensitive polymericsubstrate to form a laminated medical device construct by conducting athermal/pressure laminating step within about 10 minutes after theextrusion of the polymer film wherein said film has a crystallinity ofabout 10% or less and is laminated onto the substrate at a temperatureof about 120° C. or lower, such that the substrate is not damaged ordegraded and the film is effectively laminated to the substrate.

Another aspect of the present invention is a method of manufacturing alaminated medical device construct. A semicrystalline polymer film isextruded, the polymer film having a melting point temperature of 140° orhigher, a glass transition temperature above 25° C., and acrystallinity.

The polymer film is laminated to a thermally sensitive polymericsubstrate to form a laminated medical device construct by conducting athermal/pressure laminating step within about 10 minutes after theextrusion of the polymer film wherein said film has a crystallinity ofabout 10% or less and is laminated onto the substrate at a temperatureof about 120° C. or lower, such that the substrate is not damaged ordegraded and the film is effectively laminated to the substrate andwherein the laminated polymer film has an achievable crystallinity of atleast about 10%.

Yet another aspect of the present invention is a method of laminating apolymer film to a thermally sensitive polymeric substrate. Initially, anabsorbable polymer having a melt temperature is transferred to a hopperof a melt extruder outfitted with a slit die, with a barrel and dietemperature within the range of about 10° C. above the melt temperatureof the said absorbable polymer. The absorbable polymer is extrudedthrough said slit die, thereby forming a film. The film is drawn betweenabout 0.8× to about 10× such that the film has a thickness between 0.01mil and 10 mil. In the time interval between 0 and 10 minutes followingthe film extrusion contact is provided between the freshly extrudedpolymeric film having crystallinity of about 10% or less, and thethermally sensitive polymeric substrate. Then, the film and substrateare heat pressed to form a laminated construct at temperatures of 120°C. or lower.

Still yet another aspect of the present invention is a laminated medicaldevice construct made using any of the above-described methods.

DETAILED DESCRIPTION OF INVENTION

As used herein, the term “thermally sensitive polymeric substrate” isdefined to mean a polymeric substrate in the form of mesh or non-wovenor woven porous structure that undergoes chemical degradation or variousphysical distortions (e.g., shrinkage) upon being subjected torelatively high processing temperatures, such as temperatures of 140° C.or higher. Although it is preferred that the polymer films be made fromabsorbable polymers, in an alternate embodiment the polymer films may bemade from non-absorbable polymers.

The term “achievable crystallinity of the laminated film” as used hereinis defined to mean a maximum level of crystallinity that a polymericfilm can achieve by applying various thermal and processing means, suchas annealing.

The present invention is directed toward novel lamination methodssuitable for a semicrystalline, polymeric film exhibiting a high meltingpoint of 140° C. or higher, and having a glass transition temperature of25° C. or lower. In a preferred embodiment, the polymeric film isabsorbable. Such films may be laminated onto non-woven or woven,absorbable or non-absorbable polymer substrates, in particular thermallysensitive substrates, wherein the lamination is conducted at moderateprocessing temperature of 120° C. or lower. Another aspect of thepresent invention is a novel lamination method suitable for absorbable,semicrystalline, polymeric film exhibiting a melting point of 140° C. orhigher, and a glass transition temperature higher than 25° C., with anachievable crystallinity level of 10% or higher in the laminatedpolymeric film. In a preferred embodiment, the polymeric film isabsorbable. Such films may be laminated onto non-woven or woven,absorbable or non-absorbable polymer substrates, in particular thermallysensitive substrates, wherein the lamination is conducted at moderateprocessing temperature of 120° C. or lower.

The films made from the copolymers useful in the practice of the presentinvention may be used in a variety of medical applications includingtissue separating barriers, reinforcing buttress materials, hemostasis,drug delivery and adhesion prevention. The films can be laminated withother devices (such as meshes and other textiles) to form multilayerstructures.

In one embodiment, the film layer is made from a polymer material thatis a semi-crystalline, absorbable polymer having the melting point above140° C. In another embodiment, the film layer is made from a polymermaterial having a melting point temperature above 150° C., morepreferably more than 180° C. In another embodiment, the film layer ismade from a polymer material having a glass transition temperature ofless than about 25° C. In another embodiment of the process of thepresent invention, the film layer is made from a polymer material thatis a semi-crystalline, absorbable polymer having a melting point above140° C. and having a glass transition temperature of greater than about25° C., with an achievable crystallinity level in the laminated film of10% or higher.

The present invention is also directed to a hemostatic compositestructure having a bioabsorbable fabric or non-woven substrate having atleast two major oppositely facing surface areas and a polymer-based filmthat is laminated on at least one major surface of said substrate.Hemostasis is achieved by applying a composite structure onto a woundsite wherein a major surface of the substrate without the film layer isapplied onto the wound site. The bioabsorbable fabric substrate can bean oxidized polysaccharide and/or the non-woven substrate can be madefrom bioabsorbable, non-cellulosic derived polymers. The polymer basedfilm can be a conventional bioabsorbable polymer, such as abioabsorbable polymer selected from the group consisting ofpoly(ethoxyethylene diglycolate-co-glycolide), poly(lactide),poly(glycolide), poly(amino acids) and copolymers and terpolymersthereof. This also includes homopolymers and copolymers of lactideand/or glycolide with lower melting components including caprolactone,p-dioxanone, trimethylene carbonate (TMC), polyethylene glycol, andvarious polyether ester formulations. In one embodiment, the substrateis made from oxidized regenerated cellulose and the top coat film is acopolymer, preferably 75/25 poly(glycolide-co-epsilon caprolactone). Ina particularly preferred embodiment, the film has a thickness in therange of about 0.1 to 10 mils. In another embodiment, the polymer filmmade be made for a non-absorbable conventional polymer such aspolypropylene, polyethylene, polyethylene terephthalate, Nylon, etc.

The laminated composite structures of the present invention canoptionally further include a bioactive agent, such as a hemostaticagent, including hemostatic agents such as procoagulant enzymes,proteins and peptides, prothrombin, thrombin, fibrinogen, fibrin,fibronectin, heparinase, Factor X/Xa, Factor VIINIIa, Factor IX/IXa,Factor XI/XIa, Factor XII/XIIa, tissue factor, batroxobin, ancrod,ecarin, von Willebrand Factor, collagen, elastin, albumin, gelatin,platelet surface glycoproteins, vasopressin and vasopressin analogs,epinephrine, selectin, procoagulant venom, plasminogen activatorinhibitor, platelet activating agents, synthetic peptides havinghemostatic activity, derivatives of the above and any combinationthereof. In one embodiment, the hemostatic agent is selected from thegroup consisting of thrombin, fibrinogen and fibrin.

The composite structure including a polymeric film and a substrate oftenexhibits better handling properties for surgical applications andsettings. Many fabric or non-woven based hemostats do not have idealhandling characteristics as they wrinkle and fold during surgicalprocedures especially in the presence of blood or other fluids. Thesubstrate/film composites of the present invention minimize suchbehavior. Additionally, the presence of film improves the mechanicalstrength and pliability of the fabric or non-woven substrate basedmaterials, enhancing their suitability for use in laparoscopicprocedures. In laparoscopic procedures, the composite is expected to bepushed through the trocar and sprung open into the body cavity moreeasily than either the substrate or film components individually.

The composite structures of the present invention often exhibit greaterpropensity and/or ability to stay in place during surgical proceduresrelative to existing hemostatic devices. For example, some fabric basedproducts when used in multiple layers, or those in non-woven form maydisintegrate or their parts may migrate during the application process.A substrate/film composite architecture of the present invention helpsto maintain the physical integrity of the hemostatic materials, so itcannot fall prematurely to pieces, curve, or migrate during theprocedure. Another advantage of the composite structures is that thedevice can be sutured in place.

The composite structure devices made from the method of the presentinvention also provide for the potential to use the film component foradditional surgical functionality, such as to provide tissue support, tohelp in wound healing and/or to act as delivery carrier for bioactiveagents.

Polymers useful in preparing the fabric or non-woven substrates in thelaminated composite structures of the present invention include, withoutlimitation, collagen, calcium alginate, chitin, polyester,polypropylene, polysaccharides, polyacrylic acids, polymethacrylicacids, polyamines, polyimines, polyamides, polyesters, polyethers,polynucleotides, polynucleic acids, polypeptides, proteins, poly(alkylene oxide), polyalkylenes, polythioesters, polythioethers,polyvinyls, polymers comprising lipids, and mixtures thereof. Preferredfibers comprise oxidized regenerated polysaccharides, in particularoxidized regenerated cellulose.

Preferably, oxidized polysaccharides are used to prepare wound dressingsof the present invention. More preferably, oxidized cellulose is used toprepare fabrics used in wound dressings of the present invention. Thecellulose either may be carboxylic-oxidized cellulose, or may bealdehyde-oxidized cellulose, each as defined and described herein. Evenmore preferably, oxidized regenerated cellulose is used to preparefabric substrates used in wound dressings of the present invention.Regenerated cellulose is preferred due to its higher degree ofuniformity versus cellulose that has not been regenerated. Regeneratedcellulose and a detailed description of how to make regenerated oxidizedcellulose is set forth in U.S. Pat. Nos. 3,364,200 and 5,180,398, thecontents each of which is hereby incorporated by reference as if setforth in its entirety. As such, teachings concerning regeneratedoxidized cellulose and methods of making same are well within theknowledge of one skilled in the art of hemostatic wound dressings.

Substrates, or fabrics utilized in conventional hemostatic wounddressings, such as Surgicel® absorbable hemostat; Surgicel Nu-Knit®absorbable hemostat; Surgicel SNoW® Absorbable Hemostat; and Surgicel®Fibrillar absorbable hemostat; all available from Johnson & JohnsonWound Management Worldwide, a division of Ethicon, Inc., Somerville,N.J., a Johnson & Johnson Company, as well as Oxycel® absorbablecellulose surgical dressing from Becton Dickinson and Company, MorrisPlains, N.J., all may be used in preparing wound dressings according tothe present invention. In certain embodiments, wound dressings of thepresent invention are effective in providing and maintaining hemostasisin cases of severe bleeding. As used herein, severe bleeding is meant toinclude those cases of bleeding where a relatively high volume of bloodis lost at a relatively high rate. Examples of severe bleeding include,without limitation, bleeding due to arterial puncture, liver resection,blunt liver trauma, blunt spleen trauma, aortic aneurysm, bleeding frompatients with over-anticoagulation, or bleeding from patients withcoagulopathies, such as hemophilia. Such wound dressings allow a patientto ambulate quicker than the current standard of care following, e.g. adiagnostic or interventional endovascular procedure.

The novel lamination processes of the present invention will useconventional pressure lamination process equipment and conventional filmextrusion process equipment. The film extrusion process equipment willbe operated at a sufficient temperature, pressure and extrusion speed toeffectively provide for a desired film and output rate for a givenpolymer. For example, the temperature of the extrusion process equipmentmay be maintained at a temperature typically 100° C. to about 300° C.,more typically 120° C. to about 250° C., and preferably about 160° C. toabout 220° C. The film output rate for the process of the presentinvention will typically range from about 1 fpm to about 2,000 fpm, moretypically about 5 fpm to about 100 fpm, and preferably about 6 fpm toabout 20 fpm. The thickness of the film extruded in the process of thepresent invention will be sufficient to provide effective properties tothe laminate structure. Such properties include tensile strength,tear-resistance and stiffness. Typically the film thickness will rangefrom about 0.1 mils to about 10 mils, more typically about 0.2 mils toabout 5.0 mils, and preferably about 1.0 mils to about 3.0 mils. Theextruder pressure will typically be about 100 psi to about 5,000 psi,more typically about 500 psi to about 3,000 psi, and preferably about1,000 psi to about 2,000 psi.

After extrusion from the process equipment the extruded film ispreferably rolled up on a take-up roll with adjacent layers separated bya silicone release paper. The extruded film is then cut to lengths on aconventional cutting apparatus. The cut film is then either brought to alamination station or stored under nitrogen. The film is laminated to asuitable substrate using a conventional lamination instrument usingsufficient heat and pressure to provide for effective lamination of thefilm to the substrate. The time between the film extrusion and thelamination step will typically be about 5 seconds to about 10 minutes,more typically about 1 minute to about 8 minutes, and preferably about 2minutes to about 5 minutes. The lamination temperature will typically beabout 60° C. to about 140° C., more typically about 80° C. to about 130°C., and preferably about 100° C. to about 120° C. The lamination(Godet's speed) will typically be about 0.1 fpm to about 10 fpm, moretypically about 0.2 fpm to about 5.0 fpm, and preferably about 0.5 fpmto about 2.0 fpm.

If desired, the extruded film may be moved to a lamination instrumentwithout the intermediate step of rolling and cutting the film. In thisvariant of the process, the time between extrusion of the film and thelamination step will typically range from about 1 second to about 10seconds, more typically about 2 seconds to about 6 seconds, andpreferably about 3 seconds to about 5 seconds. After lamination in thiscontinuous process, the laminate may be rolled or cut into discretesections

The extruded polymeric films at the time of lamination need to havecrystallinity level of about 0% to about 10%, more preferably between 0%and 6%, and most preferably between 0% and 4%.

The novel laminating methods of the present invention and the laminatedmedical device constructs made from such processes have many advantages.The advantages include that no adhesive layer/film is needed forbonding, that a low processing temperature (120° C. or below) can beused to bond an absorbable or non-absorbable polymer film to a thermallysensitive substrate, which will prevent distortion and shrinkage of thesubstrate and minimize chemical degradation. The lack of an additionalbonding layer will reduce the risk of adverse tissue reactions (lessdegradation products released such as free acids), improvebiocompatibility, and decrease device stiffness—improve pliability. Theuse of method of the present invention will also significantly decreaseproduction costs and greatly simplify the manufacturing steps of such amedical device.

The following examples are illustrative of the principles and practiceof the present invention, although not limited thereto:

Example 1 Synthesis of the Segmented 75/25 Gly/Cap Copolymer

The segmented copolymer used in this example was made by the methodpreviously described in the paper entitled, “Monocryl® Suture, a NewUltra-Pliable Absorbable Monofilament Suture” Biomaterials, Volume 16,Issue 15, October 1995, Pages 1141-1148. Its synthesis was alsodescribed in the patent literature such as U.S. Pat. Nos. 5,133,739 Aand 8,278,409 B2. The disclosures of these references is incorporatedherein by reference

The final dried resin was a segmented A-B-A type copolymer having 75mole % polymerized glycolide and 25 mole % polymerized ε-caprolactoneunits as determined by the nuclear magnetic resonance, NMR method. Thedried resin exhibited an inherent viscosity, IV of 1.71 dL/g, asmeasured in hexafluoroisopropanol at 25° C. and at a concentration of0.10 g/dL. Gel permeation chromatography, GPC analysis showed a weightaverage molecular weight of approximately 85,000 Daltons. The glasstransition temperature, T_(g), of the dried resin was 4.4° C., themelting point was 194° C., and the heat of fusion, ΔH_(m), was 45.3 J/gas determined by Differential Scanning calorimetry, DSC using first heatdata and a heating rate of 10° C./min. Wide Angle X-ray Diffraction,WAXD analysis revealed that the dried resin was 45 percent crystalline.

Example 2 Selected Calorimetric Properties of the Dried Resin of Example1

DSC measurements were conducted using a model Q20-3290 calorimeter fromTA Instruments (New Castle, Del.) equipped with automatic sampler. Inindividual experiments, the dried, heat treated copolymer resin asdescribed in Example 1 was placed into DSC pans, quenched below minus(−) 60° C., and heated at the constant heating rate of 10° C./min todetermine its calorimetric properties (first heat properties); theseincluded the glass transition temperature, T_(g), the melting point,T_(m) and the heat of fusion, ΔH_(m). From the second heat measurements(resin was melted at 240° C. and then quenched below −60° C.), valuesfor T_(g), T_(m), T_(c) (crystallization temperature), and ΔH_(m) wereobtained that are independent from the previous heat treatment history.Data obtained using calorimetry measurements are displayed in Table 1.

TABLE 1 DSC Results during the First and Second Heat Runs on theCopolymer of Example 1 used to Describe the Present Invention FirstHeat, DSC Second Heat, DSC T_(g) T_(m) ΔH_(m) T_(g) T_(c) ΔH_(C) T_(m)ΔH_(m) Example (° C.) (° C.) (J/g) (° C.) (° C.) (J/g) (° C.) (J/g) 14.4 194 45.3 8.4 63.5 33.3 189 34.3

Crystallization characteristics were also assessed by the isothermalcrystallization method. Isothermal crystallization kinetics analysis ofthe copolymer of Example 1 was conducted using the DSC technique. Thedried, heat-treated copolymer resin, as described in Example 1, wasplaced into a DSC pan and completely melted at 240° C. for 2 minutes toremove any nucleation sites present in the sample. Subsequently, testedmaterials were rapidly cooled/quenched (cooling rate of −60° C./min) tothe desired crystallization temperatures. The isothermal method assumesthat no crystallization occurs before the sample reaches the testtemperature; the data obtained supported this assumption.Crystallization behavior of the resin was characterized over a widerange of temperatures, between 50° C. and 110° C. Isothermalcrystallization kinetics (at constant temperature) were monitored as achange in heat flow as a function of time. The isothermal heat flowcurve was integrated to determine the crystallinity parameters. It isworth noting that the isothermal DSC runs were made in randomized orderto avoid any bias.

The development of crystallinity with time can be accessed from thedegree of crystallization, α, which is expressed by the ratio

$\begin{matrix}{\alpha = {\frac{\Delta \; {Ht}}{\Delta \; H\; \infty} = \frac{\int_{0}^{t}{\frac{dQ}{dt}{dt}}}{\int_{0}^{\infty}{\frac{dQ}{dt}{dt}}}}} & (1)\end{matrix}$

where dQ/dt is the respective heat flow; dH_(t), the partial areabetween the DSC curve and the time axis at time t; and dH_(∞), the totalarea under the peak and corresponds to the overall heat ofcrystallization. The degree of crystallization a, is then thecrystalline volume fraction developed at time t.

After performing the integration of the heat flow/time curve, thecrystallization half-time, t₁₁₂, can be determined. The crystallizationhalf-time is the time needed to reach 50 percent crystallinity of thetotal amount developed during the isothermal run. In order to expresscrystallization kinetics, a reciprocal crystallization half-time waspresented as a function of crystallization temperature. The data fromisothermal measurements are shown in Table 2 below. The fastest kineticsfor the examined resins was observed at approximately 100° C.

TABLE 2 DSC Results during the Isothermal crystallization Runs on theCopolymer of Example 1 used to Describe the Present InventionTemperature t_(1/2) 1000/t_(1/2) Slope ΔH_(C) (° C.) (min) (min⁻¹) [W/(g× min)] (J/g) 50 No detected crystallization by DSC 55 Crystallizationdetected but difficult to quantify 60 22.0 45.5 0.00065 25.1 65 16.261.7 0.00129 18.8 70 13.0 76.9 0.00260 29.2 75 12.5 80.0 0.00318 32.2 8010.8 92.6 0.00530 33.3 85 9.4 106.5 0.00744 34.2 90 8.5 117.6 0.0101335.1 95 8.2 122.0 0.01116 35.5 100 7.1 140.8 0.01266 34.4 105 7.9 126.60.01234 36.0 110 9.0 111.1 0.01031 36.5

Example 3 Film Formation by the Melt Extrusion of the Resin of Example 1

The melt film extrusion of the resin of Example 1 was carried out usinga melt extruder Model KN125 manufactured by Davis Standard Corp.,Pawcatuck, Conn. 06379, U.S.A, outfitted with a film die. A die gap of 6mils was used in all film extrusion runs. Extruder temperaturesthroughout the different barrel zones ranged from 180 to 210° C., withthe die temperature kept at 220° C. The screw speed was set to 15.8 rpmfor 1-mil thick film with the linear speed of the pull out rollmaintained at 10.4 fpm. Similarly, for the 2-mil thick film the screwspeed was 19.1 rpm, while the linear speed of the pull out roll wasmaintained at 6.0 fpm. During film collection, a silicone release paperdispensed from a roll stand was used to separate the film layers beingwound on the take-up roll. After extrusion, the film with correspondingsilicone release paper was cut to convenient lengths and either broughtto the lamination instrument immediately after extrusion, or storedunder nitrogen for a longer period of time. The thicknesses of the filmsproduced were determined to be 1.0 and 2.0 mil.

Example 4 Examination of the Crystallization Properties of the FilmsMade in Example 3

The calorimetric properties of the unannealed and annealed films of theExample 3 were determined using the first and the second heat DSCmethods. Summary of the results is shown in Table 3 below.

TABLE 3 Thermal (Calorimetric) Properties of Unannealed and Annealed2-mil Extruded Film from Example 3 First Heat T_(g) T_(C) (° C.)/ T_(m)ΔH_(m) % Film ID Description (° C.) ΔH_(C) (J/g) (° C.) (J/g)/ Cryst.**EX. 3 - Unannealed film from 6.5 none 191.3 45.9 46 Unannealed Example 3stored at 25° C. for 48 hours EX. 3 - Annealed film from 3.0 none 191.546.8 47 Annealed Example 3 @ 105° C./8 hrs Second Heat* T_(g) T_(C) (°C.)/ T_(m) ΔH_(m) Film ID Description (° C.) ΔH_(C) (J/g) (° C.) (J/g)EX. 3 - Unannealed film from 7.5 63.9/32.4 191.0 39.9 Unannealed Example3 stored at 25° C. for 48 hours EX. 3 - Annealed film from 7.7 63.5/35.8191.4 39.9 Annealed Example 3 @ 105° C./8 hrs *The second heat DSCmeasurements were started by melting the resin at 240° C. for 2 minutes,with a subsequent quench (−60° C./min) to −60° C., followed by theconstant heating scan at 10° C./min **The percent crystallinity wascalculated from the heat of fusion of 100% crystalline PGA material(ΔH_(m) = 12 KJ/mole, which is equivalent to 103 J/g); [refs.:Biomedical Engineering Fundamentals by Joseph D. Bronzino, Donald R.Peterson; Wound Closure Biomaterials and Devices edited by Chih-ChangChu, J. Anthony von; Biomaterials: Principles and Practices edited byJoyce Y. Wong, Joseph D. Bronzino, Donald R.; Biotextiles as MedicalImplants edited by M W King, B S Gupta, R Guidoin; The BiomedicalEngineering Handbook 1 by Joseph D. Bronzino; Surfaces and Interfacesfor Biomaterials edited by P Vadgama]

As indicated in Table 3, both unannealed and annealed films made inExample 4 contain relatively high level of crystallinity (46% and 47%,respectively), as well as high melting points (both around 191° C.) asdetermined from the first heat measurement. From the second heat scanboth films showed lower level of crystallinity (around 40%). This is dueto the fact that during the experiment, the thermal history was firsterased (sample was brought into amorphous phase), followed by the stepin which the crystallinity was developed only during the heating scanfrom the quench with relatively fast heating rate of 10° C./min.

In order to understand further the crystallization kinetics of thesefilms, we conducted the following set of experiments. The piece of thefilm made in Example 3 was placed in a DSC pan, heated to 240° C. fortwo minutes to erase any thermal history, and then brought quickly toroom temperature, where it spent a specified amount of time developingcrystal morphology. After this “dwelling” period, the sample was heatedat 10° C./min to above its melting point, 240° C. During this heatingstep (first heat measurement), additional crystallization will occurfollowed by the subsequent melting transition. The difference betweenthe peak areas under the heat of fusion (melting transition) and theheat of crystallization is directly proportional to the amount ofcrystallinity that a sample developed by being exposed to roomtemperature. The summary of data from this set of experiments is givenin Table 4 below. The last column in Table 4 shows the amount ofcrystallinity developed during the residence time at room temperaturefor a given sample.

TABLE 4 Isothermal Crystallization Study of 75/25 Gly/Cap Copolymerresin of Example 1 by DSC Method as a Function of Residence Time at RoomTemperature First heat* Time spent at T_(c) ΔH_(c) T_(m) ΔH_(m) ΔH_(m) −ΔH_(c) % Polymer ID 22° C. (min) (° C.) (J/g) (° C.) (J/g) (J/g)Cryst.** EX 3-5 min 5 93.6 32.2 191.1 36.6 4.4 4.5 EX 3-10 min 10 92.330.6 192.6 37.0 6.4 6.6 EX 3-30 min 30 89.9 29.8 191.5 39.6 9.8 10.1 EX3-120 min 120 88.5 28.5 191.4 39.3 10.8 11.1 EX 3-16 hrs 960 62.5 24.0191.2 39.9 15.9 16.4 *The first heat DSC measurements were started bymelting the resin at 240° C. for 2 minutes, with a subsequent quench(−60° C./min) to 22° C., and isothermal dwelling at that temperature fora given amount of time, followed by the constant heating scan at 10°C./min **The percent crystallinity was calculated from the heat offusion of 100% crystalline PGA material (ΔH_(m) = 12 KJ/mole, which isequivalent to 103 J/g); [refs.: Biomedical Engineering Fundamentals byJoseph D. Bronzino, Donald R. Peterson; Wound Closure Biomaterials andDevices edited by Chih-Chang Chu, J. Anthony von; Biomaterials:Principles and Practices edited by Joyce Y. Wong, Joseph D. Bronzino,Donald R.; Biotextiles as Medical Implants edited by M W King, B SGupta, R Guidoin; The Biomedical Engineering Handbook 1 by Joseph D.Bronzino; Surfaces and Interfaces for Biomaterials edited by P Vadgama]

As shown in Table 4, the amount of crystallinity that films were able todevelop at room temperature was relatively small (less than 7%) duringthe 10 minutes or shorter residence time. However, with longer dwelling,the amount of crystallinity progressively increased. In addition,samples that had longer residence time at room temperature exhibitedfaster or easier crystallization during the first heating scan. This isindicated in the third column in Table 4, as the crystallization peakshifted accordingly to lower temperatures.

Example 5 Lamination of Composite Structures Having Different Substratesand a Semi-Crystalline Film Made from 75/25 Gly/Cap Mole %(Non-Inventive Example)

Films made from the copolymer resin of Example 1 having thickness of 1and 2 mil (described in Example 3) were laminated onto a variety of ORCbased substrates, available from Ethicon Inc., under the trade name ofSurgicel Classic®, Surgicel NuKnit®, Surgicel Snow®, as well as apolypropylene (PP)-based mesh for hernia repair applications. The filmswere aged or matured at room temperature; the elapsed time from theactual film extrusion process to the time of lamination was set to be atleast 48 hours or longer. The lamination was done using the heating setof Godets with the nipping roll combination. Laminations were performedat various Godet's temperatures ranging from 120 to 200° C. The rollspeed was generally kept between 0.5 and 1 FPM for both 1-mil and 2-milfilms. It is important to mention that the low temperature lamination ishighly desired to keep oxidized regenerated cellulose (ORC) materialsfree of degradation, as well as for polypropylene (PP) meshes to avoidany heat related distortions. For ORC line of products the temperatureof 120° C. or below is considered safe for lamination, while 145-150° C.is considered upper temperature limit for polypropylene-based meshes.

All attempts to laminate aged 75/25 Gly/Cap films (1 and 2-mil) onto anysubstrate at temperatures lower than 150° C. failed due to immediatedelamination (lack of bonding). This is due to the fact that the meltingpoint of the film was 191° C. There were some partial melting andbonding of the film on substrates at temperatures higher than 150° C.,but soon delamination occurred during handling. Most importantly,ORC-based substrates turned yellowish, indicating the onset ofdegradation processes, while PP mesh heavily distorted due to extensiveshrinkage.

Example 6 Lamination of Composite Structures Having Different Substratesand Freshly Extruded Low Crystallinity Films Made from 75/25 Gly/CapMole % at Low Processing Temperatures (Inventive Example)

As used herein, the term “freshly extruded” is defined to mean anabsorbable, semi-crystalline polymeric film that has been laminated on asubstrate within 10 minutes or less following its extrusion step. Inorder to examine the lamination of a 75/25 Gly/Cap film immediatelyafter extrusion step described earlier in Example 3, the piece of therectangular polymer film exiting the last set of extrusion Godet's wascut and brought to the lamination instrument described in Example 4. Aseries of lamination procedures were conducted next on each substrateusing low Godet's temperature of 120° C. at the following timeintervals: 2, 5, 10, and 30 minutes from the end of film extrusion.

Unexpectedly, all film/substrate combinations that were marked with thetime intervals 2, 5 and 10 minutes exhibited perfect laminations(bonding) at a low processing temperature of 120° C. However, certaintest combinations did not produce optimal results (partial delaminationwas observed) that were processed 30 min after film extrusion. Thesamples that were observed to produced good lamination (2, 5, and 10minutes) were subsequently placed in the stability chamber supplied withthe nitrogen flow at room temperature for 72 hours to develop additionalcrystal morphology. Following 72-hour room temperature aging thefilm/ORC film/PP-mesh composites were examined for handlingcharacteristics.

Produced laminated composites made using the process of the presentinvention exhibited excellent handling properties, and no delaminationof 75/25 Gly/Cap films were observed in any of the prepared combinationsmarked 2, 5, and 10 minutes. In addition, no distortion or wrinkling ofthe ORC or PP fabric was observed. Using extensive physical treatments,including repeated bending procedures, pulling and other subjectivehandling operations, the film/ORC and film/PP structures did not tear orshowed any sign of damage. Finally, due to low lamination temperature of120° C., no discoloration was observed in any of the ORC fabric.

Although this invention has been shown and described with respect todetailed embodiments thereof, it will be understood by those skilled inthe art that various changes in form and detail thereof may be madewithout departing from the spirit and scope of the claimed invention.

We claim: 1-11. (canceled)
 12. A method of making a laminated medicaldevice construct, comprising: a) extruding a semicrystalline polymerfilm having a melting point temperature of 140° C. or higher, a glasstransition temperature greater than 25° C., and crystallinity, b)laminating the polymer film directly to a thermally sensitive polymericsubstrate to form a laminated medical device construct by conducting athermal/pressure laminating step within about 10 minutes after the filmhas been extruded wherein the film has a crystallinity of about 10% orless in order to laminate said film onto a substrate at a temperature ofabout 120° C. or lower, wherein the substrate is not damaged and thefilm is effectively laminated to the substrate and wherein the laminatedpolymer film has an achievable crystallinity of at least about 10%. 13.The method of claim 12, wherein the substrate is selected from the groupconsisting of non-woven, woven and mesh.
 14. The method of claim 12wherein the polymer film comprises a polymer selected from the groupconsisting of homopolymers of glycolide or lactide, their copolymers,copolymers of lactide or glycolide as major components with one or moreother components including caprolactone, poly(p-dioxanone); trimethylenecarbonate (TMC), polyethylene glycol, and polyether ester formulations.15. The method of claim 12, wherein the substrate comprises a materialselected from the group consisting of collagen, calcium alginate,chitin, polyester, polypropylene, polysaccharides, polyacrylic acids,polymethacrylic acids, polyamines, polyimines, polyamides, polyesters,polyethers, polynucleotides, polynucleic acids, polypeptides, proteins,poly (alkylene oxide), polyalkylenes, polythioesters, polythioethers,polyvinyls, polymers comprising lipids, oxidized regenerated cellulose,and mixtures thereof.
 16. The method of claim 12, wherein the polymerfilm comprises a polymer selected from the group consisting ofpolypropylene, polyethylene, polyethylene terephthalate, and Nylon. 17.The method of claim 12, wherein the lamination is performed off-line.18. The method of claim 12, wherein the lamination is performed in-linereel-to-reel.
 19. The method of claim 12, wherein the extruded film isrolled and cut into pieces prior to lamination to the substrate.
 20. Amedical device construct made by the method of claim
 12. 21. A method oflaminating a polymer film to a substrate, comprising: a) transferringthe a polymer having a melt temperature of 140° C. or higher to a hopperof a melt extruder outfitted with a slit die, with a barrel and dietemperature within the range of about 10° C. above the melt temperatureof the said absorbable polymer; b) extruding said polymer through saidslit die, thereby forming a film; c) drawing the film between about 0.8×to about 10× such that the film has a thickness between 0.01 mil and 10mil; d) in the time interval between 0 and 10 minutes following the filmextrusion under step c), wherein the polymer film has a crystallinity ofabout 10% or less, providing contact between the freshly extrudedpolymeric film and a polymeric substrate; and, e) heat pressing the filmand substrate to form a laminated construct at temperatures of 120° C.or lower.
 22. The method of claim 21, wherein the substrate comprises apolymeric substrate selected from the group consisting of non-woven,woven and mesh.
 23. The method of claim 21 wherein the polymer filmcomprises a polymer selected from the group consisting of homopolymersof glycolide or lactide, their copolymers, copolymers of lactide orglycolide as major components with one or more other componentsincluding caprolactone, poly(p-dioxanone); trimethylene carbonate (TMC),polyethylene glycol, and polyether ester formulations.
 24. The method ofclaim 21, wherein the polymer film comprises a polymer selected from thegroup consisting of polypropylene, polyethylene, polyethyleneterephthalate, and Nylon.
 25. The method of claim 21, wherein thepolymer film comprises a copolymer of glycolide and epsilon-caprolactonein the molar ratio of about 75 to about 25%, respectively.
 26. Themethod of claim 21, wherein the substrate comprises a material selectedfrom the group consisting of collagen, calcium alginate, chitin,polyester, polypropylene, polysaccharides, polyacrylic acids,polymethacrylic acids, polyamines, polyimines, polyamides, polyesters,polyethers, polynucleotides, polynucleic acids, polypeptides, proteins,poly (alkylene oxide), polyalkylenes, polythioesters, polythioethers,polyvinyls, polymers comprising lipids, oxidized regenerated cellulose,and mixtures thereof.
 27. The method of claim 21, wherein the laminationis performed off-line.
 28. The method of claim 21, wherein thelamination is performed in-line reel-to-reel.
 29. The method of claim25, wherein the film crystallinity changes from about 0 to about 10% inthe first 30 minutes after extrusion, and above 20% for a dwell/agingtime longer than 24 hours.
 30. The method of claim 21, wherein theextruded film is rolled and cut into pieces prior to lamination to thesubstrate.
 31. The method of claim 21, wherein the laminated polymerfilm has an achievable crystallinity of at least about 10%.
 32. Amedical device construct made by the method of claim 21.